Excited States and Free Radicals in Biology and Medicine——Contributions from Flash Photolysis and Pulse Radiolysis

Excited states and free radicals are involved in the normal physiology of living systems; in pathological processes including lipid peroxidation, inflammation, Parkinson's disease, cancer, and ageing; in the mechanism of action of drugs, such as quinone antitumour agents, and in photochemotherapies such as the PUVA therapy of skin diseases and PDT of cancer. The chief aim of this text is to introduce the reader to this rapidly expanding field, which lies at the borderlines of physics, chemistry, biology, pharmacology, and medicine, and, in particular, to explore how time—resolved spectroscopic methods have found solutions at the molecular level to biological and medical problems.     

On the origin of SARS-CoV-2——The blind watchmaker argument

正In the comparison with SARS-CoVof 2003, SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive. By the blind watchmaker argument, such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.     

Jure Piskur (1960—2014)

<正>Following a short struggle against an aggressive cancer,Prof.Jure Piskur(Fig.1),a professor of molecular genetics at Lund University(LU),Sweden,and the University of Nova Gorica(UNG),Slovenia,died in his home in Lund on 18 May 2014.He leaves behind his lifelong partner and wife,Judita Gartner,and their sons,Jan and Jure.Jure Piskur was born in 1960 in Slovenia,at that time part of Yugoslavia.Even when Jure’s research led him to many countries and the last quarter of a century to Scandinavia,he always kept close contact with his home country.He was proud to have participated in the Slovenian independence movement,which led to its international recognition as a sovereign state in     

Inducible resistance to Fas—mediated apoptosis in B cells

Apoptosis produced in B cells through Fas(APO-1,CD95) triggering is regulated by signals derived from other surface receptors:CD40 engagement produces upregulation of Fas expression and marked susceptibility to Fas-induced cell death,whereas antigen receptor engagement,or IL-4R engagement,inhibits Fas killing and in so doing induces a state of Fas-resistance,even in otherwise sensitive,CD40-stimulated targets.Surface immunoglobulin and IL-4R utilize at least partially distinct path ways to produce Fas-resistance that differentially depend on PKC and STAT6,respectively.Further,surface immunoglobulin signaling for inducible Fas-resistance bypasses Btk,requires NF-κB,and entails new macromolecular synthesis.Terminal effectors of B cell Fas-resistance include the known anti-apoptotic gene products,Bcl-XL and FLIP,and a novel anti-apoptotic gene that encodes FAIM (Fas Apoptosis Inhibitory Molecule).faim was identified by differential display and exists in two alternatively spliced forms;faim-S is broadly expressed,but faim-L expression is tissue-specific.The FAIM sequence is highly evolu tionarily conserved,suggesting an important role for this molecule throughout phylogeny.Inducible resistance to Fas killing is hypothesized to protect foreign antigen-specific B cells during potentially hazardous interactions with FasL-bearing T cells,whereas autoreactive B cells fail to become Fas-resistant and are deleted via Fas-dependent cytotoxicity.Inadvertent or aberrant acquisition of Fas-resistance may permit autoreactive B cells to escape Fas deletion,and malignant lymphocytes to impede anti-tumor immunity.     

Applications - Some Influences of Engineering Ideas on Biology—— Being the fifth in a series of essays on the materials of nature

Ideas from engineering have helped the understanding of biological organisms for thousands of years. However, the mechanical aspects of biological materials and structures can, if properly interpreted and analysed, lead to a deeper understanding of the biology of organisms. Such an approach, although always current in some form, is nevertheless subject to the vagaries of fashion and the availability of analytical techniques. At present we are in a period of upturn. Areas of interest are deployable structures （applications in aerospace）, palaeontology （how little do we need to know in order to create a credible biosphere） and food science （we need a rational approach to the mechanics of food）.     

A Note from Editorial Board——for reviews of eukaryotic cell evolution

Last July, an old friend of Editor-in-Chief Dr. Zhen YAO, Dr. Jing Yan LI, who has been studying for years the origin of cell nucleus, visited Shanghai, and they made some discussion about his views on the importance of molecular biology approach to eukaryotic cell evolution and its possible bearing to the progress of contemporary     

The 3rd Symposium on Animal Models of Primates——The Application of Non-Human Primates to Basic Research and Translational Medicine

<正>In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases,animal models using different experimental animals,such as rodents,Drosophila,Caenorhabditis elegans,and zebrafish,have been established and used widely for many     

Construction,expression and characterization of the engineered antibody against tumor surface antigen,p185^c—erbB—2

The c-erbB-2 proto-oncogene encodes a 185kD protein p185,which belongs to epidermal growth factor receptor family.Amplification of this gene has been shown to correlate with poor clinical prognosis for certain cancer patients.The monoclonal antibody A21 which directed against p185 specifically inhibits proliferation of tumor cells overexpressing p185,hence allows it to be a candidate for targeted therapy.In order to overcome several drawbacks of murine MAb,we cloned its VH and VL genes and constructed the single-chain FV(scFv)through a peptide linker.The recombinant scFv A21 was expressed in Escherichia coli and purified by the affinity column.Subsequently it was characterized by ELISA,Western blot,cell immunohistochemistry and FACS.All these assays showed the binding activity to extracellular domain(ECD)of p185.Based on those properties of scFvA21,we further constructed the scFv-Fc fusion molecule with a homodimer form and the recombinant product was expressed in mammalian cells.In a series of subsequent analysis this fusion protein showed identical antigen binding site and activity with the parent antibody.These anti-p185 engineered antibodies have promised to be further modified as a tumor targeting drugs,with a view of application in the diagnosis and treatment of human breast cancer.     

The Second International Symposium on Programmed Cell Death Shanghai,China,Sept.1—3,2002

This major international apoptosis conference in Asia intends to bring scientists fro different parts of world to present and discuss most current advances in apoptosis research.The topics to be covered include:lymphocyte cell death,apoptosis mechanisms,developmental/physiological cell death,extracellular matrix and cell death,cell death and cancer,biochemistry and molecular biology of cell death genes and anti-death genes.     

Proteins binding to the 5‘—flanking regualtory elements of the human β—globin gene

The binding of nuclear proteins prepared from mouse erythroid tissue in different developmental stages to the 5‘-flanking regulatory elements of human β-globin gene,two negative control regions(NCR1,-610to-490 bp;NCR2,-338,to-233bp),was identified.Two stage specific protein factors corresponding to embryonic and fetal stages were found to be capable of binding to NCR2.These data provided evidence that the cis acting elements of the 5‘-flanking region might be involved in the developmental control of β-globin gene and NCR2 might be responsible in art for the silence of β-glolbin gene in the embryonic and fetal stages.     

Activation—induced cell death in B lymphocytes

Upon encountering the antigen(Ag),the immune system can either develop a specific immune response of enter a specific state of unresponsiveness,tolerance.The response of B cells to their specific Ag can be activation and proliferation,leading to the immune response,or anergy and activation-induced cell death(AICD),leading to tolerance.AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR).BCR engagement initiates several signaling events such as activation of PLCγ,Ras,and PI3K,which generally speaking,lead to survival.However,in the absence of survival signals(CD40 or IL-4R engagement),BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases,expression of pro-apoptotic genes,and inhibition of pro-survival genes.The complex interplay between survival and death signals determines the B cell fate and, consequently,the immune response.     

Capitalizing on multi-element interactions through bal-anced nutrition——A pathway to improve nitrogen use efficiency in China,India and North America

A viable option for increasing nitrogen (N) use efficiency and mitigation of negative impacts of N on the environment is to capitalize on multi-element interactions through implementation of nutrient management programs that provide balanced nutrition. Numerous studies have demonstrated the immediate efficacy of this approach in the developing regions like China and India as well as developed countries in North America. Based on 241 site-years of experiments in these countries, the first-year N recovery efficiency (RE) for the conventional or check treatments averaged 21% while the balanced treatments averaged 54% RE, for an average increase of 33% in RE due to balanced nutrition. Effective policies to promote adoption are most likely those that enable site-specific approaches to nutrient management decisions rather than sweeping, nation-wide incentives supporting one nutrient over another. Local farmers, advisers and officials need to be empowered with tools and information to help them define necessary changes in practices to create more balanced nutrient management.     

A prourokinase-RGDS chimera——Construction, expression and characterization

A tetrapeptide, RGDS, was inserted into proUK kringle domain G118-L119 by the construction of a mutant proUK-RGDS gene. The gene was expressed in the baculovirus expression system. Immunoaffinity chromatography was used to purify the chimera and protein with purity over 90% was achieved. The chimera was tested for its platelet membrane binding function and showed a calcium-dependent platelet binding activity. Amidolytic activity of the chimera was tested. The result indicated that specific amidolytic activity of plasmin activated chimera was 62000 IU/mg, comparable to the previously reported 65 355 IU/mg of plasmin activated natural proUK. Activation of plasminogen by the chimera after plasmin treatment followed Micbieal-Menten kinetics, and the Km was 0.97 μmol/L, which was also comparable to 1.64 μmol/L of native urokinase. The chimera also showed intensive ability to inhibit platelet aggregation in vitro. These results indicate that this chimera might be useful as a bifunctional thrombolytic agent.     

The effects of DNA intercalators on chromatin of chicken red blood cells——differential extraction on nonhistone proteins

Taking advantage of the effects on DNA secondary structure of two DNA-intercalators,ethidium bromide and chloroquine,we used each of them to treat nuclei from both mature erythrocytes and reticulocytes of chicken,as an alternative approach to study the relationships between DNA secondary structure,nuclear proteins and chromatin structure.We presented results of differential extraction of nuclear proteins from nuclei with DNA-intercalators,as well as preliminary characterization of these proteins.A 45kd protein is the major component in fractions extracted by both intercalators from nuclei from either mature erythrocytes or reticulocytes and seems to be a DNA-binding protein.Furthermore,from current concepts of functional aspects of DNA conformation and structural heterogeneity in chromatin and nuclear proteins,we have discussed both the significance of our results as well as technical aspects of this approach.     

Effect of Bcl—2 and caspase—3 on calcium distribution in apoptosis of HL—60 cells

Apoptosis manifests in two major execution programs downstream of the death signal:the caspase pathway and organelle dysfunction.An important antiapoptosis factor,Bcl-2 protein,contributes in caspase pathway of apoptosis.Calcium,an important intracellular signal element in cells,is also observed to have changes during apoptosis,which maybe affected by Bcl-2 protein.We have previously reported that in Harringtonine (HT) induced apoptosis of HL-60 cells,there‘s change of intracellular calcium distribution,oving from cytoplast especially Golgi‘s apparatus to nucleus and accumulating there with the highest concentration.We report here that caspase-3 becomes activated in HT-induced apoptosis of HL-60 cells,which can be inhibited by overexpression of Bcl-2 protein.No sign of apoptosis or intracellular calcium movement from Golgi‘s apparatus to nucleus in HL-60 cells overexpressing Bcl-2 or treated with Ac-DEVD-CHO,a specific inhibitor of caspase-3.The results indicate that activated caspase-2 can promote the movement of intracellular calcium from Golgi‘s apparatus to nucleus,and the process is inhibited by Ac-DEVD-CHO(inhibitor of caspase-3),and that Bcl-2 can inhibit the movement and accumulation of intracellular calcium in nucleus through its inhibition on caspase-3.Calcium relocalization in apoptosis seems to be irreversible,which is different from the intracellular calcium changes caused by growth factor.     

Advance in a terrestrial biogeochemical model—DNDC model

Global climate change is one of the most important issues of contemporary environmental safety. Quantifying regional or global greenhouse gas (GHG) emissions and searching for appropriate mitigation measures have become a relatively hot issue in international global climate change studies. The high temporal and spatial variability of GHG emissions from soils makes their field measurement at regional or national scales impractical. To develop emission factors for a wide range of management practices such as those given in the Intergovernmental Panel on Climate Change Tier I methodology are often considered as a convenient technique to estimate emissions, but these can result in substantial errors when applied to specific geographical regions. Accordingly, considering the complexity of greenhouse gas production in soils, process-based models are required to quantify and predict the GHG emissions, and also interpret the intricate relationships among the gas emissions, the environmental factors and the ecological drivers. Several detailed biogeochemical process-based models of GHG emissions have been developed and accepted in recent years to provide regional scale estimate of GHG emissions and assess the mitigation measures. Among these the DNDC (Denitrification–Decomposition) model, as a process-based biogeochemical model, is capable of predicting the soil fluxes of all three terrestrial greenhouse gases: nitrous oxide (N₂O), carbon dioxide (CO₂), and methane (CH₄), as well as other important environmental and economic indicators such as crop production, ammonia (NH₃) volatilisation and nitrate NO₃^- leaching. Originally developed as a tool to simulate GHG emissions generated from agro-ecosystem, DNDC has since been expanded to include ecosystems such as rice paddies, grazed pastures, forests, and wetlands, and the model has attracted worldwide attention to simulate carbon and nitrogen biogeochemical cycles occurring in global ecosystems. This paper introduces the scientific basis underlying the modeling of greenhouse gas emissions from terrestrial soils, brings together the worldwide research undertaken on a wide range of ecosystems to test and verify, improve and modify, and apply the DNDC model to estimate GHG emissions from these systems, and furtherly sums up the advantages and disadvantages of the model for providing a reference for the application and development of the model. Most studies showed that there was a good agreement between the simulated and observed values of CO₂, CH₄ and N₂O emissions from arable, forest and grassland fields at different geographical locations over the world. However, some discrepancies still existed between observed and simulated seasonal patterns of CH₄ and N₂O emissions. Moreover, the DNDC model was mainly tested against experimental data on GHG emissions, but there were a few validations on NO₃^- leaching, soil water dynamics, NH₃ volatilisation which could greatly impact the GHG emissions. With the high development of society and economy, China had been facing a huge challenge between food production and environmental protection. Therefore, it was an urgent task to search optimal measures for optimizing land resource use, increasing crop productivity and reducing adverse environmental impacts. Process-based biogeochemical modeling, as with DNDC, can help in identifying optimal strategies to meet the needs. In future, the DNDC model need to not only improve the capability of predicting the GHG emissions, but also the accuracy of simulating the NO₃^- leaching and soil water dynamics for quantifying the non-point source pollution through modifying the parameters of the model or combining with other models, as SWAT model. The DNDC model will play more and more important role in future studies on global change.     

Advance in a terrestrial biogeochemical model—DNDC model

Global climate change is one of the most important issues of contemporary environmental safety. Quantifying regional or global greenhouse gas (GHG) emissions and searching for appropriate mitigation measures have become a relatively hot issue in international global climate change studies. The high temporal and spatial variability of GHG emissions from soils makes their field measurement at regional or national scales impractical. To develop emission factors for a wide range of management practices such as those given in the Intergovernmental Panel on Climate Change Tier I methodology are often considered as a convenient technique to estimate emissions, but these can result in substantial errors when applied to specific geographical regions. Accordingly, considering the complexity of greenhouse gas production in soils, process-based models are required to quantify and predict the GHG emissions, and also interpret the intricate relationships among the gas emissions, the environmental factors and the ecological drivers. Several detailed biogeochemical process-based models of GHG emissions have been developed and accepted in recent years to provide regional scale estimate of GHG emissions and assess the mitigation measures. Among these the DNDC (Denitrification–Decomposition) model, as a process-based biogeochemical model, is capable of predicting the soil fluxes of all three terrestrial greenhouse gases: nitrous oxide (N₂O), carbon dioxide (CO₂), and methane (CH₄), as well as other important environmental and economic indicators such as crop production, ammonia (NH₃) volatilisation and nitrate NO₃^- leaching. Originally developed as a tool to simulate GHG emissions generated from agro-ecosystem, DNDC has since been expanded to include ecosystems such as rice paddies, grazed pastures, forests, and wetlands, and the model has attracted worldwide attention to simulate carbon and nitrogen biogeochemical cycles occurring in global ecosystems. This paper introduces the scientific basis underlying the modeling of greenhouse gas emissions from terrestrial soils, brings together the worldwide research undertaken on a wide range of ecosystems to test and verify, improve and modify, and apply the DNDC model to estimate GHG emissions from these systems, and furtherly sums up the advantages and disadvantages of the model for providing a reference for the application and development of the model. Most studies showed that there was a good agreement between the simulated and observed values of CO₂, CH₄ and N₂O emissions from arable, forest and grassland fields at different geographical locations over the world. However, some discrepancies still existed between observed and simulated seasonal patterns of CH₄ and N₂O emissions. Moreover, the DNDC model was mainly tested against experimental data on GHG emissions, but there were a few validations on NO₃^- leaching, soil water dynamics, NH₃ volatilisation which could greatly impact the GHG emissions. With the high development of society and economy, China had been facing a huge challenge between food production and environmental protection. Therefore, it was an urgent task to search optimal measures for optimizing land resource use, increasing crop productivity and reducing adverse environmental impacts. Process-based biogeochemical modeling, as with DNDC, can help in identifying optimal strategies to meet the needs. In future, the DNDC model need to not only improve the capability of predicting the GHG emissions, but also the accuracy of simulating the NO₃^- leaching and soil water dynamics for quantifying the non-point source pollution through modifying the parameters of the model or combining with other models, as SWAT model. The DNDC model will play more and more important role in future studies on global change.     

JINKENITES——A STRANGE FOSSIL FROM EARLIEST CAMBRIAN IN W. HUBEI

A strange fossil described and illustrated in the present paper was collected by the writer in 1978 from the Huangshandong Member of the Lower Cambrian Tongying Formation in western Hubei. The material was preserved in greyish brown phosphoritic dolomites in association with elements of the Yangtze Micromolluscan Fauna, such as Tchangsichiton notabilus Yu and Sinuconus clypeus, Yu of Class Polyplacophora; Yangtzemerisma rarum Yu and Y.? cancellatum Yu of Class Merismoconchia; Yangtzeconus priscus Yu, Huangshandongoconus pileus Yu, Obtusoconus paucicostatus Yu, O. rostriptutea (Qian) and Spatuloconus rudis Yu of Class Monoplacophora; Bemella simplex Yu, Latouchlla of. memmorabilis Missarzhevsky, L. sanxiaesis Yu and L. lauta Yu of Class uncertain; Archaeospira ornata Yu, A. imbricata Yu and Cambrospira sinensis Yu of Class Gastropoda; Heraultipegma yunnanense He et Yang of Class Rostroconcbia: hyolithids and some other uncertain skeletal fossils. Although the systematic position of this peculiar fossil is unknown at present, it is inferred that this genus may be one of the typical primitive animal groups based on the characters of the shell and the spe cial spines. The shell is bilaterally symmetrical, elliptical in apical view; the dorsal side is roundly convex with three different forms of dorsal spines and several pairs of marginal spines on the anterior margin. Judged from the general morphological characters of the bilaterally symmetrical shell, these lower animals, generally speaking, have adapted themselves readily to different circumstances, and reduced resistance to any directional movement necessary for varied physiological activities. As to the function of the shell’s characteristics, the narrowly rounded side may serve as the anterior. Such a model of the body helps these animals go on with their benthonic creeping or swimming life. On the other hand, the dorsal spines are different from each other in shape, size, mode of arrangement and in number; especially, the end of the hook-shaped spines is generally curved outward, while the geniculate spines are oblique outward, and curved posteriorly all of a sudden. These structures of mechanism also provide us with the evidence that the narrowly rounded side serves as the anterior, while the opposite end as the posterior.It is of particular interest that this genus is somewhat similar to Phylum Mollusca, especially to the tryblidiids of Class Monoplacophora, in some morphological characters, such as: 1) the bilateral symmetry of the shell, 2) the outline elliptical in apical view and cap shaped in lateral view and 3) the dorsal side generally roundly convex. After careful study, it has been found that since this genus is strikingly different from monoplacopharans, may be it belongs to another interesting group of skeletal fossils. The reasons for this are: 1) in the former, there are many pairs of marginal spines on the anterior margin, while in monoplacophorans, no marginal spines can be seen; and 2) in this genus, the sculptures are different from each other in different areas, not only in shape and number, but also in the mode of arrangement, whereas in monoplacophorans, they are identical with each other in the same type and shape. Judged from the different forms of dorsal sculptures, this genus is comparatively similar to such uncertain shelly fossils as Lepidites Zhong, 1977 emend. Yu, 1987 and Xiadongoconus Yu, 1979 from the same horizon in the Yangtze Region of China, but differs from the latter two genera in the presence of marginal spines on the anterior margin. In addition, this new genus also differs from brachiopods and other skeletal fossils in the peculiar type of the shell. According to the above comparison, this genus is entirely different from all the classes of Phylum Mollusca, possibly representing another interesting group of skeletal fossils. It is impossible to determine the exact taxonomic position of this genus until more materials are available.